Figure 4.

Degradation of stromal HA increases drug penetration and TC death in the tumoroids. a) Effective permeability of MDA‐MB‐468 tumoroid MVNs after different interventions targeting stromal HA as function of intravascular pressure; n = 3. b) Vascular concentration of dextran near the tumoroids normalized to the concentration at a distance > 5 mm after intervention with HA‐ase, a CD44 blocking antibody (“CD44 block”), and a TGFβ blocking antibody (“TGFβ block”), as measured by proxy of fluorescence intensity, and c) representative confocal images of tumoroid (circles) MVNs perfused with dextran after different interventions. d) Quantification of CD44 isoforms and TGFβ in 1 mm biopsies centered at the tumoroids in the MVN devices, and e) quantification of stromal HA concentration in the tumoroids after stromal HA‐targeting interventions. f) Confocal microscopy images of SKBR3 tumoroid cryosections showing increased trastuzumab penetration after HA degradation. g) Cell death in the tumoroids as a function of combined treatment with trastuzumab + cetuximab (“mAB”) with different strategies targeting stromal HA, as measured by proxy of fluorescent SYTOX intensity. Significance assessed by one‐way ANOVA after confirming a normal distribution of the data; p < 0.05 *, p < 0.01 **, p < 0.001 ***, p < 0.0001 ****.